1. Field of the Invention
This invention relates to a process for producing diastereoisomeric 2-methyl-4-hydroxy-5-protected-hydroxy-hept-6-en-prolinolamides useful as intermediates for producing ultraviolet radiation absorbers and as intermediates in synthesizing the C.sub.10 -C.sub.18 fragment of FK-506 immunosuppressant.
2. Brief Disclosures in the Art
The novel 23-membered tricyclo-macrolide FK-506 very recently isolated and characterized by Tanaka, Kuroda, and co-workers, see JACS, 109. pp. 5031, 1987, and EPO Publication No. 0184162, has been shown to possess exceptional immunosuppressive activity. The potential usefulness of such an agent in bone marrow and organ transplantations coupled with its unique structural features has prompted many in the field to initiate an effort towards the total synthesis of FK-506. A highly diastereoselective synthesis of a protected C.10-C.18 subunit 1, in its correct absolute configuration, i.e., ##STR1## has already been achieved as reported by D. Askin, R. P. Volante, R. A. Reamer, K. M. Ryan and I. Shinkai in Tetrahedron Letters, 1988, in press.
However, what is needed is an overall general synthesis utilizing readily available starting materials which would allow the synthesis of all the possible diastereoisomers of the C.sub.10 -C.sub.18 fragment of FK-506, some of which may exhibit greater immunosuppressant activity than the naturally occurring form itself.